In this study, we aimed to clarify the role of PIM-1 in papillary thyroid carcinoma (PTC) in vitro and investigate the relationship between PIM-1 and redox proteins (NOX4, SOD2, and GPX2) at the tissue and cellular levels. As a PIM-1 inhibitor, SGI-1776 inhibited cell proliferation, colony formation, migration and induced an increase in apoptosis and reactive oxygen species in two PTC cell lines (BCPAP and TPC-1). The expressions of PIM-1, SOD2 and GPX2 were downregulated after siNOX4 exposure. Immunohistochemistry in 120 PTC patients showed that all four proteins exhibited higher expression levels in PTC tissues than in adjacent normal tissues. PIM-1 expression was related to NOX4, SOD2, and GPX2 expressions. The Cancer Genome Atlas database analysis showed the significant correlation between the expression of NOX4 and PIM-1. Our results demonstrated that PIM-1 played an important oncogenic role in PTC carcinogenesis that may be related to oxidative stress.